A group of 14 subjects, who had been identified from 261 volunteers in a 1-week screen as being able to metabolize the sweetener cyclamate to cyclohexylamine (>0.2% of a daily dose), and 31 nonconverters (<0.2% metabolism) were given calcium cyclamate tablets (equivalent to 250 mg cyclamic acid, 3 times daily) for a period of 13 weeks. The metabolism of cyclamate to cyclohexylamine was determined using twice-weekly timed (3 h) urine collections during week 1-3 and 7-13. Urine specimens were collected on all other study days to investigate day-to-day fluctuations in cyclohexylamine excretion. Analyses of the twice weekly timed urine collections showed that subjects recruited as nonconverters essentially remained nonconverters. Of the converters, three showed consistently low metabolism, five showed erratic metabolism, five showed low metabolism initially, which increased during the latter part of the study, and one subject showed consistently high metabolism throughout the study. Analysis of the day-to-day urine specimens showed marked intrasubject variability. The plasma concentrations of cyclohexylamine measured on weeks 1-3 and 7-13 reflected the urine profiles. The highest individual long-term average steady-state excretion values based on the 3-h urine collections and daily samples were 21%, 23%, 25%, 29%, 34%, and 38%. The maximum % metabolism detected in the high converters occasionally reached the value of 60% reported in previous short-term studies, but this high activity was not maintained, and was followed by periods of lower metabolism. The results of this metabolism study support an acceptable daily intake (ADI) of 0-11 mg/kg body weight per day.